Collection of Lung Fluid and Tissue Samples for Research

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This study will collect fluid and tissue specimens from the lungs and nose of healthy people and people with a history of lung infections. The specimens will be examined for differences between the two groups that may be associated with susceptibility to certain infections.

Healthy normal volunteers and people with a history of lung infections between 18 and 75 years of age who are followed at NIH may be eligible for this study.

Participants undergo the following procedures:

Medical history and physical examination.

Blood and urine tests.

Electrocardiogram (ECG) and chest x-ray.

Treadmill exercise stress test (for people over 45 years old with a history of chest pain or ECG abnormalities).

Bronchoscopy: The subject s nose and throat are numbed with lidocaine and a sedative is given for comfort. A thin flexible tube called a bronchoscope is advanced through the nose or mouth into the lung airways to examine the airways carefully.

Fluid collection during the bronchoscopy using one of the following methods:

Bronchoalveolar lavage: Salt water is injected through the bronchoscope into the lung and immediately suctioned out, washing off cells lining the airways.

Bronchial brushings: A brush-tipped wire enclosed in a sheath is passed through the bronchoscope and a small area of the airway tissue is gently brushed. The brush is withdrawn with some tissue adhering to it.

Endobronchial biopsies: Small pinchers on a wire are passed through the bronchoscope and about 1 to 2 millimeters of tissue is removed.

Nasal scrape: A small device is used to scrape along the inside of the nose to collect some cells.

This research protocol involves one or more of the following procedures in healthy volunteers and patients with known or suspected predisposition to respiratory infection who are enrolled in National Institutes of Health (NIH) protocols: 1) Adults only: bronchoscopy with sampling of bronchoalveolar lavage fluid and epithelial cells in healthy adult volunteers and patients; 2) Adults and Children: sputum induction for collection of sputum specimens; 3) Adults and Children: nasal mucosal biopsies and brushings for sampling of epithelial cells; 4) Adults and Children: measurement of nasal nitric oxide production; 5) Adults and children: collection of exhaled breath condensate; 6) Adults and children: measurement of nasal potential difference. The cellular and acellular samples will be separated, and stored or transferred to the appropriate laboratories investigating these diseases.

Alveolar macrophages are the predominant (greater than 95%) cell type present in the lavage of normal subjects. Alveolar macrophages play a central role in the initiation and propagation of lung inflammation by releasing cytokines (i.e., interleukin-1, tumor necrosis factor) and chemokines (i.e., interleukin-8, monocyte chemotactic protein, macrophage inflammatory protein) that activate other resident cells and recruit inflammatory cells to a local nidus of inflammation. Airway epithelial cells are known to release a variety of mediators as well. Thus, the interaction of cells with mediators generated by alveolar cells and bronchial epithelial cells during acute inflammation is a key element in the initiation of pulmonary inflammatory responses.

Bronchoalveolar lavage (BAL), bronchial brushings, and mucosal biopsies are standard diagnostic techniques done through the bronchoscope to obtain samples of alveolar and bronchial specimens for diagnosis of infection, malignancy, or non-infectious inflammation. Nasal mucosal scrape biopsy is a minimally invasive method of obtaining airway epithelial cells to diagnose disorders of airway clearance associated with abnormal cilia (hair-like structures on airway lining cells). Sputum induction is a routinely performed procedure to facilitate the collection of respiratory secretions (mucus) through stimulation of cough with inhalation of an aerosolized concentrated salt-water solution. Exhaled breath condensate is simply collected by breathing normally through a plastic tube inserted into a chilled cylinder. Nasal potential difference is performed by placing a small needle under the skin of the forearm that is connected to a salt solution bridge and resting a small catheter on the surface of the nose through which various salt solutions are dripped.

The objective of this protocol is to analyze bronchoalveolar lavage fluid, airway epithelial cells, sputum, and exhaled breath specimens and bedside physiologic measurements from healthy volunteers and from patients who acquire respiratory infections to look for differences in immune function and to discover new pathways of infectious disease susceptibility. We hypothesize that studying cellular responses to infection and inflammatory markers released from these cells will further our understanding of human susceptibility to respiratory tract infections.

Five hundred and fifty subjects (250 healthy volunteers and 300 patients) will undergo one or more of the following: 1) bronchoscopy with bronchoalveolar lavage, bronchial brushings, endobronchial biopsies; 2) nasal mucosal scrape and/or brush biopsies; 3) sputum inductions 4) exhaled breath condensate to obtain specimens for in vitro investigations and comparisons of both the cellular and acellular components. Bedside measurements 5) nasal nitric oxide production and 6) nasal potential difference may be done to assess epithelial cell functions in real-time.

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A smoking history of 10 pack-years or more, a current smoker, or tobacco free for less than a year.

Positive HIV status. Subjects must have a negative FDA-approved HIV blood test. [Note: Results of HIV enzyme-linked immunosorbent assay (ELISA) will be documented, but a negative HIV polymerase chain reaction (PCR) test result will be sufficient for eligibility screening of subjects with positive HIV ELISA that is due to prior participation in an HIV vaccine study]

History of allergic reaction to lidocaine, sedative medications like Valium Trademark or Versed Trademark, or narcotic medications like morphine or fentanyl

Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the past three months. (Note that use of corticosteroid nasal spray for allergic rhinitis, topical corticosteroids for an acute uncomplicated dermatitis, or short-acting beta-agonists in controlled asthmatics is not excluded).

Use of platelet inhibitors including aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) within 7 days of procedure

Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent

History of recent/acute clinically significant pulmonary compromise. This will be defined by the following criteria:

New lung infection or change in status of chronic lung infection or significant new findings on chest x-ray or CT scan

Asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past two years, or that required the use of oral or parenteral corticosteroids during the past two years

Clinically significant reactive airway disease that does not respond to bronchodilators

Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions), significant bruising or bleeding difficulties with IM injections or blood draws, or use of anticoagulant medications

Use of platelet inhibitors including aspirin and NSAIDs within 7 days of procedure or clopidogrel (Plavix TM) within 14 days of procedure or the inability to safely stop platelet inhibitors for 7-14 days prior to procedures

History of allergic reaction to lidocaine, sedative medications like Valium TM or Versed TM, or narcotic medications like morphine or fentanyl

Pregnancy or breastfeeding

Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

HEALTHY VOLUNTEER INCLUSION CRITERIA FOR NASAL MUCOSAL BIOPSY:

Greater than or equal to 10 years old

Enrolled without regard to gender, race, or ethnicity

NIH employees or non-employees eligible

Able to provide proof of identity

Able and willing to complete the informed consent process

Willing to donate blood and respiratory tract samples for storage to be used for future research

History of frequent colds or significant uncontrolled hay fever symptoms, recent or active upper respiratory tract infection, such as a cold or sinusitis, or chronic sinus infection or congestion

History of turbinectomy or significant nasal pathology that would preclude obtaining mucosal scrape biopsies or other measures

Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions), significant bruising or bleeding difficulties with IM injections or blood draws, or use of anticoagulant medications

The use of nasal steroids in the past 6 weeks is an exclusion to protocol participation.

Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent

Significant uncontrolled hay fever symptoms or recent or active upper respiratory tract infection, such as a cold or sinusitis

History of turbinectomy or significant nasal pathology that would preclude obtaining mucosal scrape biopsies or other measures

Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions), significant bruising or bleeding difficulties with IM injections or blood draws, or use of anticoagulant medications

Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.

Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent

Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent.